Aspirin-induced changes in gastric function: role of endogenous prostaglandins and mucosal damage.
The relative roles of prostaglandins and mucosal injury in aspirin-induced changes in gastric function were evaluated. Conscious rhesus monkeys received a subcutaneous injection of sodium bicarbonate or aspirin (25, 50, 100, or 150 mg/kg) and sodium bicarbonate or 150 mg/kg aspirin subcutaneously plus oral sucralfate (25 mg/kg twice a day). Gastric emptying and fluid and H+ outputs were determined during a fasting period and after an 80-ml water load using a 99mTc-diethylenetriaminepentaacetic acid dilution technique. At the end of each study, the monkeys were gastroscoped to assess mucosal damage, which was ranked blindly on a scale of 0 to 5. Biopsy samples were taken from antrum and fundus for determination of prostaglandins and histological evaluation. All doses of aspirin significantly suppressed prostaglandins in both the antrum and fundus. In contrast, the aspirin-induced increase in gastric mucosal injury was dose dependent. Aspirin also produced a dose-dependent decrease in gastric emptying that was significantly correlated with erosions scores. When aspirin-induced lesions were prevented by sucralfate, the inhibition of gastric emptying was blocked during the fasting period and was attenuated following the water load. Acid secretion was also decreased significantly by aspirin. This action was not modified by sucralfate protection, suggesting that aspirin has a direct inhibitory effect on parietal cell secretion. These data show that mucosal damage contributes significantly to the aspirin-induced changes in gastric function. Moreover, prostaglandins may play a role in the control of gastric emptying, especially during early phase of the response to a water load.
Shea-Donohue
T
T
Department of Medicine, Uniformed Services of the Health Sciences, Bethesda, Maryland.
Steel
L
L
Montcalm-Mazzilli
E
E
Dubois
A
A
D000818:Animals; D001241:Aspirin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000633:toxicity; D011453:Prostaglandins / Q000502:physiology*; D013392:Sucralfate / Q000494:pharmacology
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D013392:Sucralfate; D001241:Aspirin